Researchers Discover How AIDS Virus Lurks In Bone Marrow Cells

By GINA KOLATA

Published: November 15, 1988

LIKE termites undermining the foundation of a house, the AIDS virus erodes the very cells that support a major portion of the immune system, a new study has found.

The findings help explain why AIDS virus infections are so difficult to eradicate and why the immune system appears to be so helpless to ward off the virus, experts said.

The study showed that the virus can infect and grow in very immature bone marrow cells, which show no characteristics of the mature cells they will eventually become. As they mature, these cells change dramatically and turn into monocytes and macrophages, scavenger cells of the immune system. Infected monocytes and macrophages may fail to fight infections and may spread the virus to other immune system cells.

Dr. Thomas M. Folks of the Centers for Disease Control in Atlanta, an author of the study, said infected marrow cells might seed the virus into other parts of the body, including the brain. The infected cells develop in the marrow, then are carried by the bloodstream to the rest of the body. Finding Raises Concern

The bone marrow cell work ''is not a good finding,'' said Dr. Jeffrey Laurence of Cornell Medical College in New York, saying it makes it more difficult than ever to fight the virus.

But Dr. Folks added: ''It's good that we know the virus may be able to hide in the bone marrow. It's always good to know the pathology of any agent because that gives us the knowledge to find ways to attack it.''

Dr. Folks and his colleagues, including Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease in Bethesda, Md., extracted bone marrow cells from cadavers and separated very immature cells from the rest of the marrow. Then they added the AIDS virus to laboratory dishes containing the cells and looked for evidence that the cells were infected.

Using electron microscopy, they saw the virus inside the marrow cells. And by looking for a viral enzyme that provides a biochemical fingerprint of the AIDS virus, they obtained additional, independent evidence that the marrow cells became infected by the virus. As these cells grew in the laboratory and started to mature, they began exhibiting features of monocytes and macrophages. The researchers reported their findings Friday in Science magazine. No Signs of Infection

As the AIDS virus grew inside the bone marrow cells and the cells accumulated huge numbers of viruses inside them, the cells showed no exterior signs of infection.

''This means that the virus can reproduce itself without showing itself to the immune system to be destroyed,'' Dr. Fauci said. ''It means that, in a relatively undetected way, you can have an awful lot of virus produced.''

He said he is not sure how the virus originally enters these immature cells. Ordinarily, the virus latches onto a protein, CD4, that is on the surface of immune system cells, and the CD4 protein pulls the virus in. But Dr. Fauci and his colleagues could not find CD4 on the surfaces of immature cells, although it is possible that small numbers of CD4 proteins were present but eluded detection, Dr. Fauci said.

As the marrow cells matured, and after they were infected, CD4 proteins began appearing on their surfaces, the researchers found. Several drug companies are working on products that they hope will block AIDS infections by preventing the virus from latching onto CD4 proteins.

''What we think happens,'' said Dr. Fauci, ''and this is purely speculation, is that the virus gets in through a CD4-independent mechanism.'' He suggested that the immature marrow cells could engulf the virus. Then, he said, as the cells mature and begin producing CD4 proteins, the virus could spread more rapidly from cell to cell.

Dr. Folks added that the way the virus grows in the immature marrow cells resembles its growth in monocytes and macrophages. The virus accumulates inside the cells but does not burst out. There are indications that this sort of growth pattern may render the virus more resistant to AZT, the only drug to receive Federal approval for fighting AIDS infections, Dr. Folks said.

AZT slows the progress of AIDS but does not cure the disease. The drug has been shown effective primarily in T-4 cells of the immune system, in which the virus grows by replicating inside the cell and then exploding out. New Clues to an Insidious Virus New findings indicate that the AIDS virus can enter and multiply in immature bone marrow cells. Although it is not clear how the virus enters the cells, the research helps explain how the virus can lurk in the body, making it difficult to eradicate. The virus enters the body through blood or mucous membranes and from there infiltrates the bone marrow. As the AIDS virus multiplies inside the bone marrow cells, the cells show no exterior signs of infection. When the marrow cells mature into monocytes and macrophages, scavenger cells of the immune system, they remain infected with the virus. Infected monocytes and macrophages may fail to fight infections and may spread the virus to other immune system cells and other parts of the body, including the brain.